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Meteorin-like/Meteorin-β Is a Novel Immunoregulatory Cytokine Associated with Inflammation
Irina Ushach1,2, Gerardo Arrevillaga-Boni1,2, Gina N Heller1,2
1Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA 92697.
Abstract:
We have described a novel cytokine encoded by a gene called Meteorin-like (Metrnl). Metrnl is a small (∼28 kDa) secreted protein expressed by activated macrophages and barrier tissues (mucosa and skin). Metrnl production by bone marrow macrophages is induced by several cytokines including TNF-α, IL-17α, IL-12, and IL-4 and inhibited by IFN-γ and TGF-β. Metrnl expression in macrophages is also induced by LPS, and its levels in circulation are associated with inflammatory responses in vivo. Furthermore, Metrnl regulates the production of several cytokines and chemokines in macrophages. We have produced a Metrnl mouse, which is viable and shows normal development. However, it exhibits dysregulated cytokine production, alterations in IgG production, and is highly susceptible to LPS in a sepsis model. Furthermore, older Metrnl mice develop inflammatory lesions, suggesting that Metrnl participates in the control of inflammatory responses. Taken together, these observations indicate that Metrnl encodes a novel immunoregulatory cytokine associated with inflammatory responses that we have designated Meteorin-β.
Insights
We discovered Meteorin-like (Metrnl), a novel cytokine produced by macrophages and barrier tissues. Metrnl plays a key role in regulating immune responses and controlling inflammation.
Area of Science:
- Immunology
- Molecular Biology
Background:
- Meteorin-like (Metrnl) is a novel cytokine secreted by activated macrophages and barrier tissues.
- Its production is regulated by various pro-inflammatory and anti-inflammatory cytokines, as well as LPS.
- Metrnl levels in circulation correlate with in vivo inflammatory responses.
Purpose of the Study:
- To characterize the novel cytokine Meteorin-like (Metrnl) and its role in immune regulation.
- To investigate the function of Metrnl in vivo using a Metrnl knockout mouse model.
Main Methods:
- Gene expression analysis of Metrnl in macrophages and barrier tissues.
- Generation and phenotypic analysis of Metrnl knockout mice.
- Assessment of cytokine production, IgG levels, and sepsis susceptibility in Metrnl knockout mice.
Main Results:
- Metrnl is a secreted protein (∼28 kDa) produced by macrophages and barrier tissues.
- Metrnl knockout mice exhibit dysregulated cytokine production, altered IgG levels, and increased susceptibility to LPS-induced sepsis.
- Older Metrnl knockout mice develop inflammatory lesions, indicating a role in controlling inflammation.
Conclusions:
- Metrnl is a novel immunoregulatory cytokine involved in controlling inflammatory responses.
- Metrnl plays a significant role in maintaining immune homeostasis and preventing excessive inflammation.
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